Objective

Inclusion Criteria

Exclusion Criteria

Result

Author’s

Conclusion

BMD

BTM

Fractures

To compare the effects of discontinuing ALN treatment after 5 years vs. continuing for 10 years

Postmenopausal women

・ Age 55 - 81 years old

・ Low femoral neck BMD < −1.6) at FIT baseline

・ Assigned to receive ALN during FIT and completed at least 3 years of blinded treatment during the trial and participated in the subsequent open-label period

FLEX baseline total hip BMD < −3.5)

・ Total hip BMD at FLEX baseline ≤ FIT baseline

・ Currently receiving and planning to continue medications that may affect bone metabolism

・ Impaired renal function (SCr > 2 mg/dL)

Total hip BMD decline in ALN group was significantly lower than placebo group (−1.02% vs. −3.38%, respectively; mean difference = 2.36%, CI = 1.81% - 2.90%).

Lumbar spine was the only BMD measurement that showed an increase in BMD for the duration of FLEX for both placebo and ALN users, but was significantly greater for the alendronate group (1.52% for placebo vs. 5.26% for alendronate; mean difference of 3.74%, CI = 3.03% - 4.45%).

In all other sites, BMD decline was significantly slower in patients on ALN vs. placebo.

・ ALN users had relatively stable BTM measurements vs. placebo ・ BTM levels increased gradually in the placebo group, but remained below FIT baseline levels

No significant differences between groups for all clinical fractures (19.9% with ALN, 21.3% with PBO; RR = 0.93, 95% CI = 0.71 - 1.21);

No significant difference between groups for nonvertebral fractures (18.9% with ALN, 19.0% with PBO; RR = 1.0, 95% CI = 0.76 - 1.32);

No significant difference between groups for morphometric vertebral fractures (9.8% with ALN, 11.3% with PBO; RR = 0.86, 95% CI = 0.60 - 1.22);

Significant difference between groups for clinical vertebral fractures (2.4% with ALN, 5.3% with PBO; RR = 0.45, 95% CI = 0.24 - 0.85);

Post hoc analysis of the Fracture Intervention Trial Long-term Extension trial patients at high risk (T-score of <−2.5, but without prevalent vertebral fracture) at the time of discontinuation demonstrated an increased risk of all clinical fractures associated with a discontinuation compared with remaining on ALN therapy [16]

These results suggest that for many women, discontinuation of ALN for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.